Clinical Question

Does supplemental vitamin D reduce the risk of fracture in older adults?

Bottom Line

Vitamin D level is a very good marker of ill health but not a very good treatment target. A large study showed that supplemental vitamin D does not reduce the risk of fracture, even in people with low baseline vitamin D levels or a previous fracture. (Level of Evidence = 1b)

Synopsis

The study randomized 25,871 patients, including men 50 years and older and women 55 years and older, in a two-by-two factorial design to receive 2,000 IU of vitamin D or placebo per day, and 1,000 mg of omega-3 fatty acid or placebo per day. Patients were not selected based on their fracture risk or vitamin D levels; participants with a history of cancer, cardiovascular disease, or hypercalcemia were excluded. The primary goal of the VITAL trial was to evaluate the effect of these supplements on cancer and cardiovascular outcomes. Fractures were assessed based on patient self-reported data in an annual survey and confirmed by medical record review. The mean age of participants was 57 years, 51% were women, and 20% were Black. Approximately 25% of patients had a baseline vitamin D level less than 24 ng per mL (59.90 nmol per L), and 1.5% had levels less than 12 ng per mL (29.95 nmol per L). In each group, 42% were taking supplemental vitamin D, and those patients agreed to limit the amount they were taking to no more than 800 mg per day during the study. There was a total of 1,991 fractures in 1,551 patients, with no difference in total, nonvertebral, or osteoporotic fractures (i.e., hip, wrist, humerus, and spine). The authors did a series of prespecified subgroup analyses and found no benefit in patients in the placebo group who were not taking supplemental vitamin D or calcium or in patients with a previous fragility fracture. The mean 25-hydroxyvitamin D level was 30.7 ng per mL (76.63 nmol per L) at baseline, and there was no difference in fracture rates in different quartiles of vitamin D levels, including in patients with vitamin D levels less than 24 ng per mL (hazard ratio = 1.04; 95% CI, 0.80 to 1.36) and less than 12 ng per mL (hazard ratio = 1.03; 95% CI, 0.36 to 2.95). There were no differences among groups regarding renal stones, episodes of hypercalcemia, or other adverse events.

Study design: Randomized controlled trial (double-blinded)

Funding source: Government

Allocation: Concealed

Setting: Outpatient (any)

Reference: LeBoff MS, Chou SH, Ratliff KA, et al. Supplemental vitamin D and incident fractures in midlife and older adults. N Engl J Med. 2022;387(4):299-309.

Editor's Note: Dr. Ebell is deputy editor for evidence-based medicine for AFP and cofounder and editor-in-chief of Essential Evidence Plus, published by Wiley-Blackwell.